The OncFive: Top Oncology Articles for the Week of 8/10

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

FDA Accepts NDA for Vepdegestrant in ESR1-Mutated, ER+/HER2– Breast Cancer

The FDA has accepted a new drug application seeking the approval of vepdegestrant in patients with estrogen receptor–positive/HER2-negative, ESR1-mutated advanced or metastatic breast cancer who have previously received endocrine-based therapy. The target action date has been set for June 5, 2026. The phase 3 VERITAC-2 trial (NCT05654623) showed that vepdegestrant extended median progression-free survival to 5.0 months vs 2.1 months with fulvestrant (Faslodex) in the ESR1-mutated group (HR, 0.57; P < .001). Six-month PFS rates were 45.2% with vepdegestrant and 22.7% with fulvestrant, and objective response rates (ORRs) were 18.6% vs 4.0%, respectively. The most common adverse effects (AEs) with vepdegestrant included fatigue, liver enzyme elevations, nausea, anemia, and neutropenia. Grade 3 or higher treatment-related events occurred in 8% of patients compared with 3% for fulvestrant. Overall survival (OS) results remain immature.

FDA Approves Oncomine Dx Target Test as Zongertinib Companion Diagnostic in Nonsquamous NSCLC With HER2 TKD Mutations

The FDA has approved the Oncomine™ Dx Target Test as a companion diagnostic for identifying patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 TKD–activating mutations who may benefit from zongertinib (Hernexeos). On August 8, 2025, zongertinib received accelerated approval for adults with this mutation who have received prior systemic therapy, making it the first and only oral targeted therapy for this population. The decision was supported by findings from the phase 1 Beamion LUNG-1 trial (NCT04886804), in which patients previously treated with platinum-based chemotherapy achieved ORRs of 75% without prior HER2-targeted therapy and 44% with prior HER2-targeted antibody-drug conjugates. Zongertinib is also under evaluation in the ongoing phase 3 Beamion LUNG-2 trial (NCT06151574), where it is being compared with standard-of-care therapy in the first-line setting.

Perioperative Enfortumab Vedotin Plus Pembrolizumab Displays Positive Topline Data in MIBC

The phase 3 KEYNOTE-905/EV-303 trial (NCT03924895) showed that neoadjuvant and adjuvant enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) significantly improved event-free survival, overall survival, and pathologic complete response compared with surgery alone in patients with muscle-invasive bladder cancer who were ineligible for cisplatin-based chemotherapy. This randomized, open-label study built on the established efficacy of the combination in advanced urothelial cancer and demonstrated the first systemic approach to extend survival over surgery alone in this setting. The safety profile of the regimen was consistent with prior data for both agents, with no new safety signals reported. Full results will be presented at an upcoming medical meeting.

Imsapepimut and Etimupepimut Plus Pembrolizumab Shows Clinical Improvement in PFS for Advanced Melanoma

The phase 3 IOB-013/KN-D18 trial (NCT05155254) found that first-line treatment with adjuvanted imsapepimut and etimupepimut (Cylembio) plus pembrolizumab improved PFS vs pembrolizumab alone in advanced melanoma, although the primary end point narrowly missed statistical significance (HR, 0.77; 95% CI, 0.58-1.00; P = .056). The median PFS was 19.4 months with the combination vs 11.0 months with monotherapy, with the greatest benefit seen in patients with PD-L1–negative tumors (HR, 0.54; 95% CI, 0.3500.85). The regimen was well tolerated, with injection site reactions representing the most common AEs and no new safety signals. IO Biotech shared plans to meet with the FDA in fall 2025 to discuss a potential biologics license application submission.

Clinical Development Is Discontinued for SGR-2921 in R/R AML and Higher-Risk MDS

Schrödinger has discontinued development of the CDC7 inhibitor SGR-2921 for relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome after two treatment-related deaths occurred in a phase 1 dose-escalation study (NCT05961839). Investigators determined the agent contributed to the fatalities, prompting the company to halt the program despite early signs of monotherapy activity. Preclinical data had demonstrated potent antileukemic effects, broad activity across AML models, and synergy with standard therapies. The study was designed to assess safety, tolerability, and preliminary efficacy in approximately 50 patients. Schrödinger stated the decision reflects a commitment to patient safety, even in the face of significant unmet need.